The present invention relates to novel amido, cycloamido, carbonylamido, sulfonylamido and hydrazino derivatives of inter-phenylene-PG-type compounds. Certain of these inter-phenylene-PG-type compounds are known in the art in free acid and ester form to be structural and pharmacological analogs of the prostaglandins.
The prostaglandins are a family of 20 carbon atom fatty acids, being structural derivatives of prostanoic acid, which exhibit useful activity in a wide variety of biological systems. Accordingly, such prostaglandins represent useful pharmacological agents in the treatment and prevention of a wide variety of disease conditions.
Likewise, the known inter-phenylene-PG-type compounds represent pharmacological agents exhibiting improved utility as compared to the known prostaglandins. Most especially, these known inter-phenylene-PG-type compounds are employed in the treatment and prevention of diseases whose etiology relates to abnormal or undesirable platelet aggregation.
The preparation of the known inter-phenylene-PG-type compounds is described in the art by a variety of chemical methods. For example, U.S. Pat. No. 3,933,898, issued Jan. 20, 1976, describes the preparation of a wide variety of inter-phenylene-inter-oxa-PG-type compounds. Particularly, there are described therein the preparation of inter-phenylene-oxa-PG compounds exhibiting PGF.alpha.-, PGF.beta.-, PGE-, PGA-, and PGB-type cyclopentane ring structures. Further, inter-phenylene-PG-type compounds corresponding to the inter-phenylene-oxa-type compounds described above are described and prepared in German Offenlegungsschrift No. 2,635,838.
Moreover, in addition to the various inter-phenylene- and inter-phenylene-oxa-PG type compounds of the various cyclopentane ring structures referred to above, there are prepared in United States Ser. No. 614,242, filed Sept. 17, 1975 various inter-m-phenylene- and inter-m-phenylene-3-oxa-PG-type compounds exhibiting the following cyclopentane ring structures: PGD, 9-deoxy-PGD, and 9,10-didehydro-9-deoxy-PGD.
Finally, inter-phenylene-PG-type compounds exhibiting 11-deoxy-PGE, 11-deoxy-PGF.alpha. or 11-deoxy-PGF.beta. ring type structures are prepared from the above compounds by known methods for prostaglandin cyclopentane ring transformation. See, for example, Netherlands published application No. 7,309,856, abstracted at Derwent Farmdoc CPI No. 10695B, wherein the transformation of PGA-type compounds to corresponding 11-deoxy-PG-type compounds is described. Moreover, see Belgian Pat. No. 820,008, abstracted at Derwent Farmdoc CPI No. 22475W, describing an independent synthesis of certain inter-phenylene- and inter-phenylene-oxa-11-deoxy-PG-type compounds.
In addition to the various procedures described above for the preparation of inter-phenylene-PG-type compounds, improved processes are now available for the synthesis of such compounds in free acid or ester form. See, for example, APPENDIX I, describing an improved process for the synthesis of these compounds.
In addition to the above art, which is descriptive of methods for preparing acids or ester derivatives of certain prostaglandin type compounds, the preparation of prostaglandin-type amides is likewise accomplished by known methods. For example, see U.S. Pat. No. 3,981,868, issued Sept. 21, 1976, for description of the preparation of certain amido and cycloamido derivatives of 11-deoxy-PG-type compounds.
Further, U.S. Pat. No. 3,954,741, issued May 4, 1976, describes the preparation of certain carbonylamide and sulfonylamido derivatives of various prostaglandin analogs.
Finally, French published application No. 2,235,929, abstracted at Derwent Farmdoc CPI No. 26297W, describes the preparation of certain PG-type hydrazino derivatives.